identification-localization-functioning-gastroenteropancreatic

Identification and Localization of Functioning Gastroenteropancreatic Neuroendocrine Tumors Using [<sup>18</sup>F]F-NOTA-octreotide PET/CT

Accurate identification and localization are crucial for determining surgical strategies in patients with F-GEP-NETs, as these tumors often cause specific ...

Zhejiang University School of Medicine

Current therapies for most neurodegenerative disorders are only symptomatic in nature and do not change the course of the disease. Gene therapy plays an important role in disease modifying therapeutic strategies. Herein, we have designed and optimized a series of highly branched poly(β-amino ester)s (HPAEs) containing biodegradable disulfide units in the HPAE backbone (HPAESS) and guanidine moieties (HPAESG) at the extremities. The optimized polymers are used to deliver minicircle DNA to multipotent adipose derived stem cells (ADSCs) and astrocytes, and high transfection efficiency is achieved (77% in human ADSCs and 52% in primary astrocytes) whilst preserving over 90% cell viability. Furthermore, the top-performing candidate mediates high levels of nerve growth factor (NGF) secretion from astrocytes, causing neurite outgrowth from a model neuron cell line. This synergistic gene delivery system provides a viable method for highly efficient non-viral transfection of ADSCs and astrocytes.

Highly branched  poly(β-amino ester) delivery of minicircle DNA for transfection of neurodegenerative disease related cells.

The underwater superoleophobicity of a coating is often caused by its preferential water affinity, which, however, normally weakens the substrate adhesion property. In this work, a new strategy is reported for achieving strong underwater adhesion between a well-designed amphiphilic polyurethane coating and a diverse range of substrates while also rendering the coating surface's superoleophobicity. When the coating, which is a mixture of an amphiphilic polyurethane and a water miscible solvent, is immersed in water, the hydrophobic segments aggregate to orientate and pile along the surface of substrates via a segment orientation mechanism triggered by solvent exchange with water penetration to exert strong adhesion. At the same time, the hydrophilic segments will physically crosslink to form a hydrogel coating, endowing the substrate with underwater superoleophobicity. This work provides a facile, versatile, and scalable approach for the future design of superoleophobic coatings in a water environment.

Simultaneous Realization of Superoleophobicity and Strong Substrate Adhesion in Water via a Unique Segment Orientation Mechanism.

Inflammation is a defensive reaction for external stimuli to the human body and generally accompanied by immune responses, which is associated with multiple diseases such as atherosclerosis, type 2 diabetes, Alzheimer's disease, psoriasis, asthma, chronic lung diseases, inflammatory bowel disease, and multiple virus-associated diseases. Epigenetic mechanisms have been demonstrated to play a key role in the regulation of inflammation. Common epigenetic regulations are DNA methylation, histone modifications, and non-coding RNA expression; among these, histone modifications embrace various post-modifications including acetylation, methylation, phosphorylation, ubiquitination, and ADP ribosylation. This review focuses on the significant role of histone modifications in the progression of inflammatory diseases, providing the potential target for clinical therapy of inflammation-associated diseases.

Role of Histone Post-Translational Modifications in Inflammatory Diseases.

 The underuse of invasive fraction flow reserve (FFR) in clinical practice has motivated research towards its non-invasive prediction. The early attempts relied on solving the incompressible three-dimensional Navier-Stokes equations in segmented coronary arteries. However, transient boundary condition has a high resource intensity in terms of computational time. Herein, a method for calculating FFR based on steady-state geometric multiscale (FFR) is proposed.  A total of 154 moderately stenotic vessels (40-80% diameter stenosis) from 136 patients with stable angina were included in this study to validate the clinical diagnostic performance of FFR. The method was based on the coronary artery model segmented from the patient's coronary CTA image. The average pressure was used as the boundary condition for the inlet, and the microcirculation resistance calculated by the coronary flow was used as the boundary condition for the outlet to calculate the patient-specific coronary hyperemia. Then, the flow velocity and pressure distribution and the FFRss of each coronary artery branch were calculated to evaluate the degree of myocardial ischemia caused by coronary stenosis. Also, the FFR and FFR of all patients were calculated, and the clinically measured FFR was used as the "gold standard" to verify the diagnostic performance of FFR and to compare the correlation between FFR and FFR.  According to the FFR calculation results of all patients, FFR and FFR have a good correlation (r = 0.68,  < 0.001). Similarly, the correlation of FFR and FFR demonstrated an r of 0.75 (95%CI: 0.67-0.72) ( < 0.001). On receiver-operating characteristic analysis, the optimal FFR cut point for FFR≤0.80 was 0.80 (AUC:0.85 [95% confidence interval: 0.79 to 0.90]; overall accuracy:88.3%). The overall sensitivity, specificity, PPV, and NPV for FFR ≤0.80 versus FFR ≤0.80 was 68.18% (95% CI: 52.4-81.4), 93.64% (95% CI: 87.3-97.4), 82.9%, and 91.1%, respectively.  FFR is a reliable diagnostic index for myocardial ischemia. This method was similar to the closed-loop geometric multiscale calculation of FFR accuracy but improved the calculation efficiency. It also improved the clinical applicability of the non-invasive computational FFR model, helped the clinicians diagnose myocardial ischemia, and guided percutaneous coronary intervention.

Non-Invasive Quantification of Fraction Flow Reserve Based on Steady-State Geometric Multiscale Models.

Elemene sensitizes pancreatic cancer cells to bortezomib by enhancing proteasome inhibition via molecular patch mechanism.

A coordinated interaction between osteogenesis and the osteoimmune microenvironment plays a vital role in regulating bone healing. However, disturbances in the pro- and anti-inflammatory balance hinder the therapeutic advantages of biomaterials. In this study, a novel composite hydrogel was successfully fabricated using graphene oxide (GO)-loaded processed pyritum (PP) in combination with poly(ethylene glycol) diacrylate (PEGDA) and carboxymethyl chitosan (CMC). Subsequently, the immunomodulatory effects and bone regenerative potential of PP/GO@PEGDA/CMC were investigated. The results demonstrated that the PP/GO@PEGDA/CMC hydrogel possessed excellent mechanical properties, swelling capacity, and stability. Moreover, PP/GO@PEGDA/CMC prominently promoted M2 polarization and increased the levels of anti-inflammatory factors (interleukin (IL)-4, IL-10, and transforming growth factor-β). These beneficial effects facilitated the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Additionally, the in vivo results further verified that the implantation of PP/GO@PEGDA/CMC markedly reduced local inflammation while enhancing bone regeneration at 8 weeks post-implantation. Therefore, the results of this study provide potential therapeutic strategies for bone tissue repair and regeneration by modulating the immune microenvironment.

A graphene oxide-loaded processed pyritum composite hydrogel for accelerated bone regeneration via mediation of M2 macrophage polarization.

Epidural steroid injection (ESI) is a common therapeutic approach for managing sciatica caused by lumbar disc herniation (LDH). However, the short duration of therapeutic efficacy and the need for repeated injections pose challenges in LDH treatment. The development of a controlled delivery system capable of prolonging the effectiveness of ESI and reducing the frequency of injections, is highly significant in LDH clinical practice. In this study, we utilized a thiol-ene click chemistry to create a series of injectable hyaluronic acid (HA) based release systems loaded with diphasic betamethasone, including betamethasone dipropionate (BD) and betamethasone 21-phosphate disodium (BP) (BD/BP@HA). BD/BP@HA hydrogel implants demonstrated biocompatibility and biodegradability to matched neuronal tissues, avoiding artificial compression following injection. The sustained release of betamethasone from BD/BP@HA hydrogels effectively inhibited both acute and chronic neuroinflammation by suppressing the nuclear factor kappa-B (NF-κB) pathway. In a mouse model of LDH, the epidural administration of BD/BP@HA efficiently alleviated LDH-induced sciatica for at least 10 days by inhibiting the activation of macrophages and microglia in dorsal root ganglion and spinal dorsal horn, respectively. The newly developed HA hydrogels represent a valuable platform for achieving sustained drug release. Additionally, we provide a simple paradigm for fabricating BD/BP@HA for epidural injection, demonstrating greater and sustained efficiency in alleviating LDH-induced sciatica compared to traditional ESI and displaying potentials for clinical translation. This system has the potential to revolutionize drug delivery for co-delivery of both soluble and insoluble drugs, thereby making a significant impact in the pharmaceutical industry. STATEMENT OF SIGNIFICANCE: Lumbar disc herniation (LDH) is a common degenerative disorder leading to sciatica and spine surgery. Although epidural steroid injection (ESI) is routinely used to alleviate sciatica, the efficacy is short and repeated injections are required. There remains challenging to prolong the efficacy of ESI. Herein, an injectable hyaluronic acid (HA) hydrogel implant by crosslinking acrylated-modified HA (HA-A) with thiol-modified HA (HA-SH) was designed to achieve a biphasic release of betamethasone. The hydrogel showed biocompatibility and biodegradability to match neuronal tissues. Notably, compared to traditional ESI, the hydrogel better alleviated sciatica in vivo by synergistically inhibiting the neuroinflammation in central and peripheral nervous systems. We anticipate the injectable HA hydrogel implant has the potential for clinical translation in treating LDH-induced sciatica.

Biphasic release of betamethasone from an injectable HA hydrogel implant for alleviating lumbar disc herniation induced sciatica.

Circular RNAs (circRNAs) have garnered considerable attention in the study of various human diseases due to their ubiquitous expression and potential biological functions. This study conducts a bibliometric and visualization-based analysis of circRNA-related research in diseases, aiming to reveal the current status, hotspots and emerging trends within the field.

Bibliometric analysis of the research hotspots and trends of circular RNAs.

Despite numerous studies addressing the molecular mechanisms by which pluripotent stem cells (PSCs) maintain self-renewal and pluripotency under normal culture conditions, the fundamental question of how PSCs manage to survive stressful conditions remains largely unresolved. Post-transcriptional/translational regulation emerges to be vital for PSCs, but how PSCs coordinate and balance their survival and differentiation at translational level under extrinsic and intrinsic stress conditions is unclear.

OCT4 translationally promotes AKT signaling as an RNA-binding protein in stressed pluripotent stem cells.

The accurate and comprehensive characterization of flavor compounds in Ningxia  berry (Lycii Fructus) to provide an accurate geographical discrimination model remains unrealized. Here, a novel strategy that integrates headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) with our newly developed GC-MS data analysis software, AntDAS-GCMS, was employed for the accurate tracing of samples from typical cultivated zones of China, including Ningxia, Gansu, Qinghai, and Xinjiang province. Parameters of HS-SPME were optimized using the resolved components from AntDAS-GCMS. Information on volatile compounds (VOCs) was collected with GC-MS under the optimized HS-SPME. Raw GC-MS data files were automatically analyzed via AntDAS-GCMS to perform component resolution, time-shift correction and registration, chemometric analysis, and compound identification. A total of 275 components were screened, based on which 30 VOCs were identified. Four chemometric models were evaluated through Monte-Carlo simulation, and the partial least squares-discrimination provided the best geographical discrimination performance with the identified compounds.

Comprehensive characterization of flavor compounds in  berry by HS-SPME-GCMS combined with AntDAS-GCMS for geographical discrimination.

Our study aims to compare the differences in gut fungal community structure between pregnant women with gestational diabetes mellitus (GDM) and healthy pregnant women at 24-28 weeks of gestation, and to explore the correlation between differential fungi, clinical indicators and adverse pregnancy outcomes.

Intestinal fungal dysbiosis in gestational diabetes mellitus is associated with adverse pregnancy outcomes.

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (B-ALL) is associated with a poor prognosis. Although CD19 chimeric antigen receptor T (CAR-T) cell therapy has shown promise in this population, its long-term efficacy and safety remain unclear. To address this, we conducted a retrospective multicenter study to evaluate the long-term survival outcomes of autologous and allogeneic CD19 CAR-T cell therapies in 55 B-ALL patients who relapsed after allo-HSCT. Following CAR-T cell infusion, 37 patients (67.3%) achieved complete remission (CR). The 3-year leukemia-free survival rate among CR patients was 37.8%. The 3-year overall survival rate for both CR and non-remission patients was 36.2%. Cytokine release syndrome was the most common adverse event, occurring in 74.5% of patients. No significant differences in efficacy or safety were found between autologous and allogeneic CAR-T cell groups (all P > 0.05). This study demonstrates the promising 3-year survival and safety profile of both autologous and allogeneic CD19 CAR-T cell therapies, and further supports CD19 CAR-T cell therapy as a valuable treatment for patients with relapsed B-ALL after allo-HSCT.

Long-term follow-up of CD19 chimeric antigen receptor T cell therapy in acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation.

Article	Year
Highly branched poly(β-amino ester) delivery of minicircle DNA for transfection of neurodegenerative disease related cells. Nature communications\| PubMed ID: 31341171	2019
Simultaneous Realization of Superoleophobicity and Strong Substrate Adhesion in Water via a Unique Segment Orientation Mechanism. Advanced materials (Deerfield Beach, Fla.)\| PubMed ID: 34676921	2022
Role of Histone Post-Translational Modifications in Inflammatory Diseases. Frontiers in immunology\| PubMed ID: 35280995	2022
Non-Invasive Quantification of Fraction Flow Reserve Based on Steady-State Geometric Multiscale Models. Frontiers in physiology\| PubMed ID: 35492621	2022
Elemene sensitizes pancreatic cancer cells to bortezomib by enhancing proteasome inhibition via molecular patch mechanism. Signal transduction and targeted therapy\| PubMed ID: 36849489	2023
A graphene oxide-loaded processed pyritum composite hydrogel for accelerated bone regeneration via mediation of M2 macrophage polarization. Materials today. Bio\| PubMed ID: 37593216	2023
Biphasic release of betamethasone from an injectable HA hydrogel implant for alleviating lumbar disc herniation induced sciatica. Acta biomaterialia\| PubMed ID: 38244658	2024
Bibliometric analysis of the research hotspots and trends of circular RNAs. Heliyon\| PubMed ID: 38818139	2024
OCT4 translationally promotes AKT signaling as an RNA-binding protein in stressed pluripotent stem cells. Stem cell research & therapy\| PubMed ID: 39988663	2025
Comprehensive characterization of flavor compounds in berry by HS-SPME-GCMS combined with AntDAS-GCMS for geographical discrimination. Food chemistry: X\| PubMed ID: 40547602	2025
Intestinal fungal dysbiosis in gestational diabetes mellitus is associated with adverse pregnancy outcomes. BMC pregnancy and childbirth\| PubMed ID: 41612266	2026
Long-term follow-up of CD19 chimeric antigen receptor T cell therapy in acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation. Cytotherapy\| PubMed ID: 41830735	2026

Wenxin Wang

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